DEVELOPMENTAL CANCER THERAPEUTICS: SUMMARY The Developmental Cancer Therapeutics (DCT) Program seeks to discover and characterize critical cancer- specific metabolic pathways, identify novel therapeutic agents, and translate discoveries into effective cancer therapies and chemoprevention strategies. Three common themes unite programmatic initiatives: 1) lipid signaling and metabolism, 2) cancer stress response pathways, and 3) drug discovery and early-phase clinical trials. Fundamental discoveries have been made in the identification and mechanistic understanding of sphingolipids, prostaglandins, membrane receptors, and extra-cellular factors involved in cancer cell signaling. Support from the Hollings Cancer Center (HCC) shared resources and collaborations within and across programs has led to identification of natural and synthetic compounds that target cancer metabolism, including inhibitors of sphingosine 1-phosphate and sphingosine kinase 2, which have moved to phase 1 and 2 trials in refractory renal and liver cancers (NCT01488513, NCT0176203, and NCT02939807). New compounds and biomarkers led to statewide opportunities for therapeutic intervention and prevention of human cancers impacting the HCC catchment area, including in the socioeconomically and geographically underserved African American communities. The program of 30 members is co-led by two exceptional scientists with distinct basic and clinical backgrounds who collaboratively build a synergistic program: Besim Ogretmen, PhD, a basic scientist pioneering discoveries in lipid biology and biomarker development, and Michael Lilly, MD, a practicing physician-scientist translating fundamental discoveries into clinical trials. The total peer-reviewed direct funding base, excluding career development and training grants is $4.8M, with 22 active NCI-funded projects ($3.5M), and a growing number of multi-institutional and programmatic awards (P20 GM103542; P01 CA203628; U54 MD010706, U54 CA210962). Rich collaborative research opportunities in DCT laboratories have enhanced the entire education and career development continuum, from undergraduates in minority colleges to graduate students, postdoctoral fellows, and junior clinical members (K12 CA157688). These cancer-focused efforts culminated in 238 publications since 2013, of which 34% represent intraprogrammatic, 37% interprogrammatic, and 67% multi-institutional collaborations, including 33 seminal discoveries and translational breakthroughs published in top-tier journals (IF >10) such as in N Engl J Med, Nature, Nat Comm, Sci Transl Med (2), Cell, Cell Metab, Mol Cell, JAMA (2), JCI (3), JCO (8), and Lancet Oncol (3). With investments in cutting edge technologies, targeted faculty recruitment, and new interprogrammatic team-based funding initiatives supported by new HCC leadership, the DCT Program is poised to advance scientific discovery, target identification and pre-clinical development, and clinical trials implementation in the HCC catchment area and beyond.